Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.
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SUBMITTER: Zimmermann E
PROVIDER: S-EPMC4564522 | biostudies-literature | 2015 Apr
REPOSITORIES: biostudies-literature
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Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.
Zimmermann E E Ängquist L H LH Mirza S S SS Zhao J H JH Chasman D I DI Fischer K K Qi Q Q Smith A V AV Thinggaard M M Jarczok M N MN Nalls M A MA Trompet S S Timpson N J NJ Schmidt B B Jackson A U AU Lyytikäinen L P LP Verweij N N Mueller-Nurasyid M M Vikström M M Marques-Vidal P P Wong A A Meidtner K K Middelberg R P RP Strawbridge R J RJ Christiansen L L Kyvik K O KO Hamsten A A Jääskeläinen T T Tjønneland A A Eriksson J G JG Whitfield J B JB Boeing H H Hardy R R Vollenweider P P Leander K K Peters A A van der Harst P P Kumari M M Lehtimäki T T Meirhaeghe A A Tuomilehto J J Jöckel K-H KH Ben-Shlomo Y Y Sattar N N Baumeister S E SE Smith G Davey GD Casas J P JP Houston D K DK März W W Christensen K K Gudnason V V Hu F B FB Metspalu A A Ridker P M PM Wareham N J NJ Loos R J F RJF Tiemeier H H Sonestedt E E Sørensen T I A TIA
Obesity reviews : an official journal of the International Association for the Study of Obesity 20150305 4
Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 ...[more]
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Project description:BackgroundThe A-allele of the single nucleotide polymorphism (SNP), rs9939609, in the FTO gene is associated with increased fatness. We hypothesized that the SNP is associated with morbidity and mortality through the effect on fatness.Methodology/principal findingsIn a population of 362,200 Danish young men, examined for military service between 1943 and 1977, all obese (BMI>or=31.0 kg/m(2)) and a random 1% sample of the others were identified. In 1992-94, at an average age of 46 years, 752 of the obese and 876 of the others were re-examined, including measurements of weight, fat mass, height, and waist circumference, and DNA sampling. Hospitalization and death occurring during the following median 13.5 years were ascertained by linkage to national registers. Cox regression analyses were performed using a dominant effect model (TT vs. TA or AA). In total 205 men died. Mortality was 42% lower (p = 0.001) with the TT genotype than in A-allele carriers. This phenomenon was observed in both the obese and the randomly sampled cohort when analysed separately. Adjustment for fatness covariates attenuated the association only slightly. Exploratory analyses of cause-specific mortality and morbidity prior to death suggested a general protective effect of the TT genotype, whereas there were only weak associations with disease incidence, except for diseases of the nervous system.ConclusionIndependent of fatness, the A-allele of the FTO SNP appears to increase mortality of a magnitude similar to smoking, but without a particular underlying disease pattern barring an increase in the risk of diseases of the nervous system.
| S-EPMC2639637 | biostudies-literature
Project description:Background: Higher grip strength (GS) is associated with lower mortality risk. However, whether this association is independent of adiposity is uncertain.Objective: The purpose of this study was to examine the associations between GS, adiposity, and mortality.Design: The UK Biobank study is an ongoing prospective cohort of >0.5 million UK adults aged 40-69 y. Baseline data collection (2006-2010) included measurements of GS and adiposity indicators, including body mass index (BMI; in kg/m2). Age- and sex-specific GS quintiles were used. BMI was classified according to clinical cutoffs.Results: Data from 403,199 participants were included in analyses. Over a median 7.0-y of follow-up, 8287 all-cause deaths occurred. The highest GS quintile had 32% (95% CI: 26%, 38%) and 25% (95% CI: 16%, 33%) lower all-cause mortality risks for men and women, respectively, compared with the lowest GS quintile, after adjustment for confounders and BMI. Obesity class II (BMI ?35) was associated with a greater all-cause mortality risk. The highest GS quintile and obesity class II category showed relatively higher all-cause mortality hazards (not statistically significant in men) than the highest GS quintile and the normal weight category; however, the increased risk was relatively lower than the risk for the lowest GS quintile and obesity class II category. All-cause mortality risks were generally lower for obese but stronger individuals than for nonobese but weaker individuals. Similar patterns of associations were observed for cardiovascular mortality.Conclusions: Lower grip strength and excess adiposity are both independent predictors of higher mortality risk. The higher mortality risk associated with excess adiposity is attenuated, although not completely attenuated, by greater GS. Interventions and policies should focus on improving the muscular strength of the population regardless of their degree of adiposity.
| S-EPMC6101209 | biostudies-other
Project description:Previous studies have examined the association between the fat mass and obesity-associated (FTO) gene variant and risk of cancer in diverse populations. However, the results have been inconsistent. PubMed and Embase databases were searched for the eligible publications in English language by July, 2016. The associations of FTO variants with cancer risk were estimated by calculating the pooled odds ratios and 95% confidence intervals by meta-analyses. A total of 27 publications (129,467 cancer cases and 290,633 normal controls) were included in our meta-analysis. Overall, FTO rs9939609 variant (or its proxy) was not associated with cancer risk without adjustment for body mass index, as well as additional adjustment for body mss index. However, FTO rs9939609 variant was associated with some types of cancer in the subgroup analysis. In addition, overall, there was no significant association between FTO rs1477196 variant and cancer risk regardless of adjustment for body mass index. However, FTO rs11075995 variant risk allele was associated with breast cancer risk without adjustment for body mass index, but the association disappeared with further adjustment for body mass index. This study overall does not support that the FTO variant is associated with cancer risk independently of the adiposity.
| S-EPMC5584223 | biostudies-literature
Project description:BackgroundAdiposity predicts health outcomes, but this relationship could depend on population characteristics and adiposity indicator employed. In a representative sample of 11,437 US adults (National Health and Nutrition Examination Survey, 1988-1994, ages 18-64) we estimated associations with all-cause mortality for body mass index (BMI) and four abdominal adiposity indicators (waist circumference [WC], waist-to-height ratio [WHtR], waist-to-hip ratio [WHR], and waist-to-thigh ratio [WTR]). In a fasting subsample we considered the lipid accumulation product (LAP; [WC enlargement*triglycerides]).Methods and findingsFor each adiposity indicator we estimated linear and categorical mortality risks using sex-specific, proportional-hazards models adjusted for age, black ancestry, tobacco exposure, and socioeconomic position. There were 1,081 deaths through 2006. Using linear models we found little difference among indicators (adjusted hazard ratios [aHRs] per SD increase 1.2-1.4 for men, 1.3-1.5 for women). Using categorical models, men in adiposity midrange (quartiles 2+3; compared to quartile 1) were not at significantly increased risk (aHRs<1.1) unless assessed by WTR (aHR 1.4 [95%CI 1.0-1.9]). Women in adiposity midrange, however, tended toward elevated risk (aHRs 1.2-1.5), except for black women assessed by BMI, WC or WHtR (aHRs 0.7-0.8). Men or women in adiposity quartile 4 (compared to midrange) were generally at risk (aHRs>1.1), especially black men assessed by WTR (aHR 1.9 [1.4-2.6]) and black women by LAP (aHR 2.2 [1.4-3.5]). Quartile 4 of WC or WHtR carried no significant risk for diabetic persons (aHRs 0.7-1.1), but elevated risks for those without diabetes (aHRs>1.5). For both sexes, quartile 4 of LAP carried increased risks for tobacco-exposed persons (aHRs>1.6) but not for non-exposed (aHRs<1.0).ConclusionsPredictions of mortality risk associated with top-quartile adiposity vary with the indicator used, sex, ancestry, and other characteristics. Interpretations of adiposity should consider how variation in the physiology and expandability of regional adipose-tissue depots impacts health.
| S-EPMC3511554 | biostudies-literature
Project description:OBJECTIVE:Accumulation of adipose tissue is associated with cardiometabolic risks. Although visceral adipose tissue (VAT) has been strongly implicated in this relationship, there is still some debate regarding the contribution of abdominal subcutaneous adipose tissue (SAT). The purpose of this study was to determine the contribution of abdominal SAT to cardiometabolic risk factors, independent of total and visceral adiposity. These relationships were assessed in Caucasian and African Americans. DESIGN:It is a cross-sectional analysis of the Pennington Center Longitudinal Study. SUBJECTS:Data were extracted from 1246 participants. Total body fat mass (FM) was measured by dual-energy X-ray absorptiometry, whereas abdominal VAT and SAT areas (cm(2)) were measured with computed tomography. The cardiometabolic risk factors included resting blood pressure (BP), fasting blood glucose and triglyceride concentrations and high-density lipoprotein cholesterol (HDL-C). RESULTS:Positive relationships across tertiles of VAT were seen for the participants with high glucose, high BP and low HDL-C (P<0.043). There was also a significant increase in the percentage of participants with two or more cardiometabolic risk factors across most tertiles of abdominal SAT (P<0.042). Logistic regression analysis showed that in univariate models, all adiposity measures were significantly associated with increased odds of having all risk factors in men and women. In multivariate models, VAT was significantly associated with most risk factors across gender. Abdominal SAT and FM (odds ratios (ORs) 1.3-2.1; all P<0.05) were associated with fewer risk factors after accounting for VAT. VAT (OR=5.9 and 5.3) and SAT (OR=2.0 and 1.8) were both associated with higher odds of the presence of two or more cardiometabolic risk factors in both males and females (P<0.001). CONCLUSION:The data suggest that abdominal SAT is not protective against unfavorable cardiometabolic risk profiles. These conclusions were consistent across ethnic groups.
| S-EPMC3302129 | biostudies-literature
Project description:BackgroundPrognostic significance of adiposity, at the time of cancer diagnosis, on survival is not clear. Body mass index (kg?m-2) does not provide an appropriate assessment of body composition; therefore, the concept of the 'obesity paradox' needs to be investigated based on the prognostic significance of fat and muscle. Independent prognostic significance of adipose tissue in predicting mortality, importance of visceral and subcutaneous adiposity in the presence and absence of sarcopenia on survival, was investigated.MethodsAdiposity markers including total adipose index (TATI), visceral adipose tissue index (VATI) and subcutaneous adipose tissue index (SATI) were estimated for 1473 gastrointestinal and respiratory cancer patients and 273 metastatic renal cell carcinoma patients using computed tomography. Univariate and multivariate analysis to determine mortality hazard ratios (HR) were conducted using cox proportional hazard models.ResultsLow SATI (SATI <50.0?cm2?m-2 in males and <42.0?cm2?m-2 in females) independently associated with increased mortality (HR: 1.26; 95% CI: 1.11-1.43; P<0.001) and shorter survival (13.1 months; 95% CI, 11.4-14.7) compared to patients with high SATI (19.3 months; 95% CI, 17.6-21.0; P<0.001). In the presence of sarcopenia, the longest survival was observed in patients with high subcutaneous adiposity.ConclusionsSubcutaneous adipose tissues appear to associate with reduction in mortality risk demonstrating the prognostic importance of fat distribution. The effect of sarcopenia on survival was more pronounced in patients with low subcutaneous adiposity.
| S-EPMC5520211 | biostudies-literature
Project description:ImportanceThe 1-year standardized mortality ratio (SMR) of bullous pemphigoid (BP) has been reported as 2.15 to 7.56 and lower in the US than in Europe.ObjectiveTo estimate the worldwide 1-year SMR of BP.Data sourcesPubMed, Embase, Cochrane Library, Google Scholar, Lissa, and gray literature (eg, medRxiv) were screened for studies of BP published from inception to June 10, 2020, with review of reference lists.Study selectionRetrospective and prospective studies reporting 1-year all-cause mortality rate in patients with BP and providing age statistics (eg, mean [SD]).Data extraction and synthesisTwo reviewers independently extracted the data. The 1-year SMR was computed in studies reporting 1-year mortality by combining information on age obtained from studies with aggregate data and individual data. Risk of representativity, misclassification, and attrition bias were assessed by a custom tool.Main outcomes and measuresThe primary end point was the worldwide 1-year SMR. Secondary analysis included comparison of 1-year SMRs between continents in a meta-regression.ResultsThree studies were performed in the US (n = 260), 1 in South America (n = 45), 16 in Asia (n = 1903), and 36 in Europe (n = 10 132) for a total of 56 unique studies and 12 340 unique patients included in the meta-analysis (mean [SD] age, 77.3 [12.7] years; 55.9% women). The mean (SD) patient age in the United States was 75.6 (13.7) years; in Asia, 73.8 (13.6) years; and in Europe, 78.1 (12.3) years. The worldwide 1-year SMR was estimated at 2.93 (95% CI, 2.59-3.28; I2 = 85.6%) for all 56 studies. The 1-year SMR in the US was 2.40 (95% CI, 0.89-3.90; I2 = 86.3%) for 3 studies; in Asia, 3.53 (95% CI, 2.85-4.20; I2 = 86.3%) for 16 studies; and in Europe, 2.77 (95% CI, 2.35-3.19; I2 = 86.3%) for 36 studies. After adjustment on the expected 1-year mortality rate, the European 1-year SMR did not differ significantly from the 1-year SMR in the United States (-0.48 vs Europe; 95% CI, -2.09 to 1.14; P = .56) and Asia (0.51 vs Europe; 95% CI, -0.56 to 1.58; P = .35). Risk of attrition bias was high (>10% censorship) in 16 studies (28.6%), low in 16 (28.6%), and unclear in 24 (42.9%). Only 4 studies (7.1%) had a sampling method guaranteeing the representativity of BP cases in a population.Conclusions and relevanceAlthough heterogeneity was high and overall quality of follow-up was poor, this meta-analysis confirms the high mortality rate among patients with BP.
| S-EPMC7970384 | biostudies-literature
Project description:Personality may influence the risk of death, but the evidence remains inconsistent. We examined associations between personality traits of the five-factor model (extraversion, neuroticism, agreeableness, conscientiousness, and openness to experience) and the risk of death from all causes through individual-participant meta-analysis of 76,150 participants from 7 cohorts (the British Household Panel Survey, 2006-2009; the German Socio-Economic Panel Study, 2005-2010; the Household, Income and Labour Dynamics in Australia Survey, 2006-2010; the US Health and Retirement Study, 2006-2010; the Midlife in the United States Study, 1995-2004; and the Wisconsin Longitudinal Study's graduate and sibling samples, 1993-2009). During 444,770 person-years at risk, 3,947 participants (54.4% women) died (mean age at baseline = 50.9 years; mean follow-up = 5.9 years). Only low conscientiousness-reflecting low persistence, poor self-control, and lack of long-term planning-was associated with elevated mortality risk when taking into account age, sex, ethnicity/nationality, and all 5 personality traits. Individuals in the lowest tertile of conscientiousness had a 1.4 times higher risk of death (hazard ratio = 1.37, 95% confidence interval: 1.18, 1.58) compared with individuals in the top 2 tertiles. This association remained after further adjustment for health behaviors, marital status, and education. In conclusion, of the higher-order personality traits measured by the five-factor model, only conscientiousness appears to be related to mortality risk across populations.
| S-EPMC3755650 | biostudies-literature
Project description:BackgroundAsian Chinese are more susceptible to deposition of visceral adipose tissue (VAT) and type 2 diabetes (T2D) development than European Caucasians when matched for gender, age and body mass index (BMI). Our aims were: (i) characterise the ethnicity-specific metabolomic signature of visceral adiposity measured by dual energy X-ray absorptiometry (DXA) and fasting plasma glucose (FPG), and (ii) identify individuals susceptible to worse metabolic health outcomes.MethodsFasting plasma samples from normoglycaemic (n = 274) and prediabetic (n = 83) participants were analysed with liquid chromatography-mass spectrometry using untargeted metabolomics. Multiple linear regression adjusting for age, gender and BMI was performed to identify metabolites associated with FPG and VAT calculated as percentage of total body fat (%VATTBF) in each ethnic group. Metabolic risk groups in each ethnicity were stratified based on the joint metabolomic signature for FPG and %VATTBF and clinically characterised using partial least squares-discriminant analysis (PLS-DA) and t-tests.ResultsFPG was correlated with 40 and 110 metabolites in Caucasians and Chinese respectively, with diglyceride DG(38:5) (adjusted β = 0.29, p = 3.00E-05) in Caucasians and triglyceride TG(54:4) (adjusted β = 0.28, p = 2.02E-07) in Chinese being the most significantly correlated metabolite based on the p-value. %VATTBF was correlated with 85 and 119 metabolites in Caucasians and Chinese respectively, with TG(56:2) (adjusted β = 0.3, p = 8.25E-09) in Caucasians and TG(58:3) (adjusted β = 0.25, p = 2.34E-08) in Chinese being the most significantly correlated. 24 metabolites associated with FPG were common to both ethnicities including glycerolipid species. 67 metabolites associated with %VATTBF were common to both ethnicities including positive correlations with dihydroceramide, sphingomyelin, glycerolipid, phosphatidylcholine, phosphatidylethnolamine, and inverse correlations with ether-linked phosphatidylcholine. Participant re-stratification found greater total and central adiposity, worse clinical lipid profiles, higher serum glucoregulatory peptides and liver enzymes in normal fasting glucose (NFG) individuals with a prediabetic metabolomic profile than NFG individuals with a normoglycaemic metabolomic profile in both ethnicities.ConclusionsUntargeted metabolomics identified common and disparate metabolites associated with FPG and %VATTBF, with an ethnic-dimorphic signature for these metabolic traits. These signatures could improve risk stratification and identify NFG individuals with an adverse cardiometabolic and T2D risk profile.
| S-EPMC7667766 | biostudies-literature
Project description:Physical inactivity accentuates the association of variants in the FTO locus with obesity-related traits but evidence is largely lacking in non-European populations. Here we tested the hypothesis that physical activity (PA) modifies the association of the FTO single-nucleotide polymorphism (SNP) rs9939609 with adiposity traits in 2,656 African Americans (AA) (1,626 women and 1,030 men) and 9,867 European Americans (EA) (5,286 women and 4,581 men) aged 45-66 years in the Atherosclerosis Risk in Communities (ARIC) study. Individuals in the lowest quintile of the sport activity index of the Baecke questionnaire were categorized as low PA. Baseline BMI, waist circumference (WC), and skinfold measures were dependent variables in regression models testing the additive effect of the SNP, low PA, and their interaction, adjusting for age, alcohol use, cigarette use, educational attainment, and percent European ancestry in AA adults, stratified by sex and race/ethnicity. rs9939609 was associated with adiposity in all groups other than AA women. The SNP × PA interaction was significant in AA men (P ? 0.002 for all traits) and EA men (P ? 0.04 for all traits). For each additional copy of the A (risk) allele, WC in AA men was higher in those with low PA (?(lowPA): 5.1 cm, 95% confidence interval (CI): 2.6-7.5) than high PA (?(highPA): 0.7 cm, 95% CI: -0.4 to 1.9); P (interaction) = 0.002). The interaction effect was not observed in EA or AA women. FTO SNP × PA interactions on adiposity were observed for AA as well as EA men. Differences by sex require further examination.
| S-EPMC3293392 | biostudies-literature